PCSK9 Antibodies in Adults With Hypercholesterolemia | Journal Scan

Study Questions:

What is the efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies [PCSK9 inhibition (PCSK9i)] in adults with hypercholesterolemia?


The authors searched MEDLINE, PubMed Central, and Google Scholar; conference proceedings; and the ClinicalTrials.gov registry through April 4, 2015. They included Phase 2 or 3 randomized controlled trials (RCTs) comparing treatment using PCSK9i with no anti-PCSK9 therapy in adults with hypercholesterolemia. Prespecified primary endpoints were all-cause and cardiovascular mortality. Treatment and placebo control groups could be on ezetimibe, statins, or combination of both.


Twenty-four RCTs comprising 10,159 patients were included. Compared with no antibody, treatment with PCSK9i led to marked reductions in low-density lipoprotein cholesterol (mean difference, -47.49%; 95% confidence interval, -69.64% to -25.35%; p < 0.001), 25% reduction in lipoprotein (a), and about a 6% increase in high-density lipoprotein cholesterol. While overall mortality was very low at 0.39%, active treatment reduced all-cause mortality (odds ratio [OR], 0.45; p = 0.015) and cardiovascular mortality (OR, 0.50; p = 0.084). The rate of myocardial infarction was significantly reduced with use of PCSK9i (OR, 0.49; p = 0.030), and increases in the serum creatine kinase level were reduced (OR, 0.72; p = 0.026). Serious adverse events did not increase with administration of PCSK9 inhibition.


The authors concluded that PCSK9 antibodies seem to be safe and effective for adults with dyslipidemia.


The summary of available literature supports the safety and lack of adverse events with PCSK9 inhibitors in over 10,000 patients who were followed from 2 months to 2 years. Longer-term data in well-defined populations will be necessary to establish safety and appropriate clinical use of this expensive novel class of lipid-lowering agents.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Advanced Lipid Testing, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Azetidines, Cholesterol, Cholesterol, LDL, Cholesterol, HDL, Control Groups, Creatine Kinase, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Lipoprotein(a), Lipoproteins, HDL, Lipoproteins, LDL, Myocardial Infarction, Proprotein Convertases, Subtilisins, Primary Prevention

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